Chemotactic activity in carrageenan (0.5 mg)-induce pleural exudates was demonstrated by the chemotactic response of neutrophils in the modified Boyden chamber. Activity was proportional to exudate protein in the range of 0.75 to 1.5 mg protein per chamber (1.2 ml). The activity differed from that is rat serum or plasma in that it was stable for 30 min at 56 degree C. Indomethacin (5 mg/kg i.v.) reduced equally protein content (56%) and total chemotactic activity (58%); chemotactic activity/mg of exudate protein was unchanged. Intrapleural injection of autologous or homologous serum induced infiltration of neutrophils; and when injected in two doses to maintain protein levels comparable to those found with carrageenan, the number of neutrophils in the exudates were also comparable. In contrast to the neutrophil response to carrageenan, the response to serum was not inhibited by indomethacin. The results suggest that in the carrageenan model, indomethacin acts primarily by inhibiting plasma protein exudation and thereby, the availability of plasma precursors of chemotactic factor(s).